None listed
Conditions
Brief summary
This study is testing a new dosing schedule of Lutetium-177 PSMA (177Lu-PSMA), a radioactive treatment for men with prostate cancer that has spread and no longer responds to standard hormone therapy. The aim is to see whether giving 177Lu-PSMA more frequently at the start of treatment can overcome early resistance and improve outcomes. Who is it for? You may be eligible for this study if you are a male aged 18 or over who has prostate cancer that has spread to other parts of the body and is no longer controlled by standard hormone therapy (castration-resistant). You must have evidence of metastatic disease on imaging, a reasonable general health status (ECOG 0–2), a life expectancy of at least 12 weeks, and adequate blood and organ function. Men who have previously received modern hormone therapies such as abiraterone or enzalutamide may be eligible. Study details All participants will be randomised to either arm 1 or arm 2 with different dosing schedules. Depending on when you join the study, you will either receive 7.5 GBq or 8.5 GBq. The first 40 participants randomised on the study (both arms 1 and 2) will all receive 7.5 GBq of 177 Lu-PSMA at each dosing visit. For the next 80 participants (participants 41 – 120), anyone randomised to arm 1 on the study will receive 8.5 GBq of 177 Lu-PSMA at each dosing visit. Participants will receive 177Lu-PSMA treatment according to either the standard schedule or a more frequent dosing schedule. You will have PSMA PET/CT scans, blood tests, and other routine health checks to monitor your response and side effects. It is hoped that this study will help provide important information on whether a new dosing schedule can improve the effectiveness of 177Lu-PSMA and guide future treatment for men with advanced prostate cancer.
Interventions
Arm 1: 3 doses of [177Lu]Lu-PSMA 7.5GBq will be administered intravenously on Cycle 1 (Days 1, 3 and 15). Following this, based on the results of a week 8 PSMA-PET scan and blood PSA (ng/mL) level, a further 3 doses (10 weeks apart) will be given on Cycles 2, 3 and 4 in a biomarker guided adaptive dosing schedule. A total of 6 doses will be given.
Arm 2: 6 doses of [177Lu]Lu-PSMA 7.5GBq will be administered intravenously on a 6 weekly schedule (Cycles 1-6). A total of 6 doses will be given.
St
Arm 1: 3 doses of [177Lu]Lu-PSMA 7.5GBq will be administered intravenously on Cycle 1 (Days 1, 3 and 15). Following this, based on the results of a week 8 PSMA-PET scan and blood PSA (ng/mL) level, a further 3 doses (10 weeks apart) will be given on Cycles 2, 3 and 4 in a biomarker guided adaptive dosing schedule. A total of 6 doses will be given. Arm 2: 6 doses of [177Lu]Lu-PSMA 7.5GBq will be administered intravenously on a 6 weekly schedule (Cycles 1-6). A total of 6 doses will be given. Strategies to assess adherence to the intervention include routine safety blood tests prior to each dose and in between doses, PSA levels, and scheduled imaging with SPECT/CT post doses. The exact dose activity prepared, dispensed and administered will be documented, including time, route and any residual activity, to confirm accurate dosing.
First 40 participants randomised on the study will be administered 7.5GBq doses (Part A) and the rest of the randomised participants (41 – 120) will be administered either 8.5GBq on Arm 1 or 7.5GBq on Arm 2 doses (Part B).
Part A
- Arm 1: 3 doses of [177Lu]Lu-PSMA 7.5GBq will be administered intravenously on Cycle 1 (Days 1, 3 and 15). Following this, based on the results of a week 8 PSMA-PET and blood PSA (ng/mL) level, a further 3 doses (10 weeks apart) will be given on Cycles 2, 3 and 4 in
First 40 participants randomised on the study will be administered 7.5GBq doses (Part A) and the rest of the randomised participants (41 – 120) will be administered either 8.5GBq on Arm 1 or 7.5GBq on Arm 2 doses (Part B). Part A - Arm 1: 3 doses of [177Lu]Lu-PSMA 7.5GBq will be administered intravenously on Cycle 1 (Days 1, 3 and 15). Following this, based on the results of a week 8 PSMA-PET and blood PSA (ng/mL) level, a further 3 doses (10 weeks apart) will be given on Cycles 2, 3 and 4 in a biomarker guided adaptive dosing schedule. A total of 6 doses will be given. - Arm 2: 6 doses of [177Lu]Lu-PSMA 7.5GBq will be administered intravenously on a 6 weekly schedule (Cycles 1-6). A total of 6 doses will be given. Part B - Arm 1: 3 doses of [177Lu]Lu-PSMA 8.5GBq will be administered intravenously on Cycle 1 (Days 1, 3 and 15). Following this, based on the results of a week 8 PSMA-PET and blood PSA (ng/mL) level, a further 3 doses (10 weeks apart) will be given on Cycles 2, 3 and 4 in a biomarker guided adaptive dosing schedule. A total of 6 doses will be given. - Arm 2: 6 doses of [177Lu]Lu-PSMA 7.5GBq will be administered intravenously on a 6 weekly schedule (Cycles 1-6). A total of 6 doses will be given. Strategies to assess adherence to the intervention include routine safety blood tests prior to each dose and in between doses, PSA levels, and scheduled imaging with SPECT/CT post doses. The exact dose activity prepared, dispensed and administered will be documented, including time, route and any residual activity, to confirm accurate dosing.
Sponsors
St Vincent's Health Network
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
Male
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Written informed consent obtained prior to the initiation of study procedures. 2. Participants aged greater than or equal to 18 years. 3. Adenocarcinoma of the prostate defined by documented histopathology of prostate adenocarcinoma or, metastatic disease typical of prostate cancer on imaging with an elevated PSA. 4. Progressive disease defined as at least one of the following: a. PSA progression defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week prior and a minimum of 2.0 ng/mL. b. Radiological progression on CT or Whole Body Bone Scan (WBBS) as per PCWG3 criteria or RECIST. c. Clinical progression as determined by treating physician. 5. Evidence of metastatic disease on PSMA PET/CT and significant PSMA avidity as defined by the VISION criteria. 6. Castration-resistant disease: defined as disease progression despite castration by orchiectomy or ongoing Luteinizing Hormone-Releasing Hormone (LHRH) treatment and serum testosterone less than or equal to 1.7 nmol/L 7. Prior Androgen Receptor Pathway Inhibitor (ARPI) (e.g., abiraterone, darolutamide, apalutamide, enzalutamide) for mHSPC or mCRPC. 8. Life expectancy greater than or equal to 12 weeks 9. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. 10. Adequate organ function; documented within 28 days prior to trial registration: Haemoglobin greater than or equal to 80, Platelet count greater than or equal to 100, Neutrophils greater than 1.0 11. Willing and able to comply with all study requirements.
Exclusion criteria
1. Symptomatic or impending cord compression that has not been adequately treated and stable for greater than or equal to 4 weeks on steroid doses less than or equal to equivalent of 10mg prednisolone 2. Prior treatment with PSMA targeted radionuclide therapy. 3. Uncontrolled intercurrent illness including but not limited to; illicit drug dependency, active/recently active malignancy or psychiatric illness that could, in investigator's opinion, potentially interfere with participation in this study or places the participant at undue risk, or complicates the interpretation of safety data. 4. Inability to follow radiation safety precautions related to trial treatment.
Outcome results
None listed